Action Points

Note that this study suggests treatment should begin even earlier, when the cell count is between 350 and 500.

Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

WASHINGTON, Oct. 27 -- HIV patients have an improved mortality risk if they start therapy earlier than current guidelines suggest, a researcher said here.

Asymptomatic patients who started therapy when their CD4-positive T cell count was between 350 and 500 cells per cubic millimeter of blood did better than those who waited until the count was lower, according to Mari Kitahata, M.D., of the University of Washington in Seattle.

Those getting early treatment had a 70% lower risk of dying sooner than later compared with those who waited -- a reduction that is "meaningful and substantial," Dr. Kitahata told a late-breaking clinical trials session at the Interscience Conference on Antimicrobial Agents and Chemotherapy, held jointly with the Infectious Diseases Society of America meeting.

The finding suggests that current guidelines for starting HIV therapy aim too low, she said.

"This does impact on and differ from current guidelines and recommends treatment earlier in disease," she said. "All patients with a CD4 count 500 and below should receive anti-retroviral treatment."

Currently, Health and Human Services guidelines recommend that treatment for asymptomatic patients should start when the CD4 count falls to 350 or fewer. The 2008 guidelines of the International AIDS Society-USA Panel, released in August, also suggest starting therapy when the number falls below 350. (See: IAC: HIV Care Guidelines Expand Treatment Eligibility)

In contrast, Dr. Kitahata said, her study shows that waiting even until the cell count reaches 350 increases the risk of death. "HIV patients have less risk of dying if they start earlier than current recommendations," she said.

The finding may start the treatment pendulum swinging back in the direction of "hit early, hit hard," espoused in the early days of the area of highly active anti-retroviral therapy (HAART) when clinicians hoped aggressive treatment might result in a cure.

That hope vanished in face of the persistence of HIV, and clinicians became less aggressive in order to limit the side effects of HAART.

But evidence has been mounting that earlier treatment might avoid some of the non-AIDS morbidity associated with HIV infection and with this new data about mortality it may be time, Dr. Kitahata said, for clinicians to "hit earlier."

The finding is based on an analysis of 22 prospective HIV research cohorts from the U.S. and Canada. Dr. Kitahata and colleagues analyzed outcomes for 8,374 patients who were diagnosed between 1996 and 2006 when their CD4 cell count was between 350 and 500.

A multivariate Cox regression analysis showed that the relative hazard for death, with the early treatment group as a reference, was 1.7, with a 95% confidence interval from 1.4 to 2.1, which was significant at P<0.001.

The relative hazard remained unchanged at 1.7 when the researchers adjusted for injection drug use and hepatitis C co-infection, Dr. Kitahata said.

Although the study is not a randomized controlled trial, Dr. Kitahata said, sensitivity analyses suggest that any residual confounder would have to be very large to overturn the results.

She added that its large size and diverse population mean its results are likely generalizable to clinical practice.

"I think these are really very important data," said Dan Kuritzkes, M.D., of Brigham and Women's Hospital in Boston, who was not involved in the study.

"I think the importance of this study is that by aggregating all these North American cohorts together," he said, "they've got enough patients to have the power to see this important difference."

Dr. Kuritzkes said he thinks the data are strong enough to change practice, with the caveat that many people even now are diagnosed at a very late stage of disease, with CD4 counts in the mid-200s.

"That's because people are still being tested far too late," he said.

The study was sponsored by the NIH. Dr. Kitahata did not report any conflicts.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco

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